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EP1148880B1 - Procedes permettant de retablir ou d'accroitre l'espace disponible lors de conditions pseudo-phakiques - Google Patents

Procedes permettant de retablir ou d'accroitre l'espace disponible lors de conditions pseudo-phakiques Download PDF

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Publication number
EP1148880B1
EP1148880B1 EP00907033A EP00907033A EP1148880B1 EP 1148880 B1 EP1148880 B1 EP 1148880B1 EP 00907033 A EP00907033 A EP 00907033A EP 00907033 A EP00907033 A EP 00907033A EP 1148880 B1 EP1148880 B1 EP 1148880B1
Authority
EP
European Patent Office
Prior art keywords
eye
muscarinic
accommodation
ciliary muscle
medicament
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP00907033A
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German (de)
English (en)
Other versions
EP1148880A2 (fr
Inventor
Arlene Gwon
Elizabeth Wolde Mussie
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Johnson and Johnson Surgical Vision Inc
Original Assignee
Advanced Medical Optics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Advanced Medical Optics Inc filed Critical Advanced Medical Optics Inc
Publication of EP1148880A2 publication Critical patent/EP1148880A2/fr
Application granted granted Critical
Publication of EP1148880B1 publication Critical patent/EP1148880B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia

Definitions

  • the present invention is directed to the use of muscarinic components for the manufacture of a medicament for increasing the ability of the eye to accommodate. More particularly, the invention relates to the use of muscarinic components for the manufacture of a medicament for increasing the amounts of accommodation in mammalian eyes including artificial intraocular lenses (IOLs), more preferably IOLs which are adapted to provide accommodating movement in the eye.
  • IOLs intraocular lenses
  • the human eye includes an anterior chamber between the cornea and iris, a posterior chamber, defined by a capsular bag, containing a crystalline lens, a ciliary muscle, a vitreous chamber behind the lens containing the vitreous humor, and a retina at the rear of this chamber.
  • the human eye has a natural accommodation ability. The contraction and relaxation of the ciliary muscle provides the eye with near and distant vision, respectively. This ciliary muscle action shapes the natural crystalline lens to the appropriate optical configuration for focusing light rays entering the eye on the retina.
  • the ciliary muscle controls the shape of the natural lens through suspensory ligaments called zonules. Like most smooth muscles, the ciliary muscle has a dual innervation, receiving both sympathetic and parasympathetic fibers.
  • the contraction of the ciliary muscle is under parasympathetic or cholinergic control. While this parasympathetic control is predominant, sympathetic, or adrenergic, innervation opposes the cholinergic control and plays a lesser role in enabling relaxation of the ciliary muscle.
  • a conventional, monofocal IOL can be placed in the posterior chamber.
  • IOLs include an optic or lens body adapted to focus light toward the retina of the eye.
  • fixation members or haptics are coupled to the optic and function to fix the IOL in the eye.
  • Such a conventional IOL has very limited, if any, accommodating ability.
  • the wearer of such an IOL continues to require the ability to view both near and far (distant) objects. Corrective spectacles may be employed as a useful solution.
  • IOLs with accommodating movement along the optical axis of the eye as an alternative to shape changing. Examples of such attempts are set forth in Levy U.S. Patent 4,409,691 and several patents to Cumming, including U.S. Patents 5,674,282 and 5,496,366.
  • Such so called accommodating IOLs include an optic or lens body adapted to focus light toward the retina and a movement assembly, having various configurations, coupled to the optic and adapted to cooperate with the eye, for example, with the ciliary muscle of the eye, to move the optic axially to obtain some degree of accommodation.
  • the lenses of the patents noted above in this paragraph are biased to be located in the posterior-most position in the eye under rest or resting conditions.
  • the ciliary muscle contracts and the lens moves forwardly (positive accommodation). In the absence of ciliary muscle contraction, the lens moves rearwardly to its posterior-most resting position.
  • IOLs One problem that exists with such IOLs is that they often cannot move sufficiently to obtain the desired accommodation.
  • muscarinic components for the manufacture of a medicament for increasing the amounts of accommodation in mammalian eyes which include IOLs have been discovered.
  • the medicaments manufactured in accordance with the present invention take advantage of the discovery that muscarinic components, such as muscarinic agonists and muscarinic antagonists, assist or facilitate the action of the ciliary muscle and associated zonules so that the IOL in the eye is effectively moved to provide accommodation, for example, both positive (near) accommodation and negative (far) accommodation.
  • Treatment with a muscarinic component for example, administering an effective amount of muscarinic component to an eye, preferably is effective to provide increased accommodating movement of the IOL in the eye relative to a substantially identical IOL in a substantially identical eye which is not treated with the muscarinic component.
  • the present methods are convenient to practice and provide outstanding accommodation results, often with substantially no adverse effects to the mammal wearing the IOL.
  • methods for increasing the amount of accommodation in an eye of a mammal which includes an artificial IOL comprise administering to the mammal an effective amount of a muscarinic component, such as a muscarinic agonist or a muscarinic antagonist.
  • This administering step preferably is effective to increase tonic contraction of the ciliary muscle of the eye.
  • the medicaments manufactured in accordance with the present invention are particularly effective in situations in which the IOL is adapted to move axially in the eye to provide at least some degree of accommodation.
  • the muscarinic agonist/antagonist preferably is administered in a pharmaceutically acceptable formulation, for example, in a non-irritating sterile solution or suspension.
  • the muscarinic agonist/antagonist more preferably is administered topically to the eye in a pharmaceutically acceptable ophthalmic formulation.
  • the muscarinic component that is the muscarinic agonist or muscarinic antagonist, may be selected to act on various muscarinic (M) receptor subtypes of the ciliary muscle.
  • the ciliary muscle acts on the lens to reshape the lens to provide the desired focus accommodation.
  • the ciliary muscle often acts to move the optic of the IOL axially in the eye to effect accommodation.
  • the ciliary muscle may be adversely affected by the lens replacement surgery.
  • the size and configuration of the artificial IOL is different from the natural lens. Because of these and other factors, the ciliary muscle benefits from assistance in providing accommodation when the eye includes an artificial IOL.
  • Increasing or enhancing the tone, for example, restoring the natural tone, of the ciliary muscle of an eye including an artificial IOL facilitates or assists the eye in providing accommodation.
  • this accommodation facilitation or assistance is provided by the administration of an effective amount of a muscarinic component, as described herein.
  • the medicaments manufactured in accordance with the present invention for increasing the amounts of accommodation in the eye of a mammal which eye includes an artificial IOL comprise administering to the mammal an effective amount of a muscarinic component, such as a muscarinic agonist or a muscarinic antagonist.
  • a muscarinic component such as a muscarinic agonist or a muscarinic antagonist.
  • the muscarinic component administered as described herein acts to at least assist or facilitate the ciliary muscle, for example, by effecting a parasympathetic response, or blocking or stimulating the parasympathetic system to obtain more effective ciliary muscle tone, in providing accommodation, for example, increased accommodation.
  • This administering step preferably is effective to increase tonic contraction of the ciliary muscle.
  • the administering step very usefully is effective to increase the tone of the ciliary muscle at a neutral resting state of the eye.
  • neutral resting state refers to the state of the eye which exists without visual stimuli, for example, in a totally darkened room or in a luminous but completely empty visual field. Such a “neutral resting state” can be considered the natural resting state of the eye.
  • the neutral resting state of the eye can be referred to as "tonic accommodation”, “space myopia” and “sky myopia”. Viewed from a different perspective, the neutral resting state of the eye (with the natural crystalline lens present) exists with the eye focused for objects in a range of about one meter to about two meters from the eye.
  • the muscarinic components administered in accordance with the present invention act on one or more muscarinic (M) receptor subtypes of the ciliary muscle.
  • M muscarinic
  • Muscarinic receptor subtypes enable selective contraction or relaxation of the circular or longitudinal fibers of the ciliary muscle by action on the M 1 - M 5 receptor subtypes.
  • the M 3 receptor subtype is the most common and is seen predominantly in the circular fibers and the M 5 receptor subtype is predominant in the longitudinal fibers. Accordingly, it is possible that the inhibition of the M 5 receptor subtype may allow the relaxation/stretching of the longitudinal fibers.
  • the compounds useful in practicing the present invention include any and all suitable muscarinic agonists or antagonists.
  • muscarinic agonists means any compound that stimulates a parasympathetic receptor subtype to generate a response.
  • Parasympatholytic agents which block the parasympathetic system are muscarinic antagonists and parasympathomimetic agents which stimulate the parasympathetic system are muscarinic agonists.
  • Neuro-effective junctions are considered cholinergic if energized by muscarinic agonists such as acetylcholine.
  • muscarinic agonists are M nonselective and are parasympathomimetic and stimulate the parasympathetic system.
  • Such muscarinic agonists include, but not limited to:
  • Muscarinic antagonists are parasympatholytic and block the parasympathetic system.
  • muscarinic antagonists include, but not limited to, in relation to M receptor subtypes:
  • Analogs of the foregoing compounds that function as muscarinic agonists are also specifically intended to be embraced by the present invention.
  • the ability of such analogs to function in accordance with the present invention can be tested easily using no more than routine experimentation.
  • the medicaments manufactured in accordance with the present invention are particularly suited for subjects who are otherwise free of indications for ophthalmic treatments utilizing a muscarinic agonist or antagonist.
  • the muscarinic components in accordance with the present invention may be administered per se or in the form of pharmaceutically acceptable salts.
  • the salts of muscarinic agonists and muscarinic antagonists should be both pharmacologically and pharmaceutically acceptable, but non-pharmaceutically acceptable salts may be conveniently used to prepare the active free compounds or pharmaceutically acceptable salts thereof.
  • the treatment of this invention can be substantially conventionally administered, consistent with known eye treatments, and while avoiding irritation, discomfort or the need for unusual application procedures.
  • compositions useful in the present invention may include any suitable formulation from which the presently useful muscarinic components may be delivered to the eye.
  • the muscarinic components useful in the present invention are topically administered or applied to the eye.
  • topical administration the muscarinic components included in the formulations contact the surface of the eye and penetrate into the deeper tissues of the eye.
  • Such formulations usually include liquid carriers and can be aqueous solutions or suspensions.
  • the muscarinic components in accordance with the present invention are provided in formulations which enhance the duration of activity of the active material on neuro-effective junctions.
  • the muscarinic components in accordance with the present invention preferably are administered in pharmaceutically acceptable ophthalmic formulations.
  • Such pharmaceutically acceptable ophthalmic formulation produces medically desirable therapeutic effects without concurrently causing clinically significant adverse effects.
  • Clinically significant effects refer to unacceptable side effects of the formulation, including either medically or cosmetically unacceptable effects. Examples of unacceptable side effects include, but are not limited to, reddening or irritated eyes, impaired long distance vision, elevated intraocular pressure, or browache.
  • the muscarinic components in accordance with the present invention are administered in therapeutically effective amounts.
  • a therapeutically effective amount is one which at least assists or facilitates the ciliary muscle in providing accommodation, for example, positive and/or negative accommodation, preferably increased accommodation, in an eye including an artificial IOL.
  • the muscarinic components are typically added to the formulations in accordance with the present invention in amounts in a range of about 0.001% and about 4% by weight of the entire formulation.
  • the muscarinic components in accordance with the present invention are preferably administered topically and delivered in a medically acceptable, substantially sterile, non-irritating ophthalmic formulation.
  • Ophthalmic formulations may contain pharmaceutically acceptable concentrations of salts, buffering agents, preservatives, viscosity modifiers, osmotic agents and delivery enhancing agents.
  • Salts which can be used include, but are not limited to, sodium chloride, zinc sulfate, and potassium chloride.
  • Buffers which can be used include, but are not limited to, boric acid and citric acid-based buffers.
  • Preservatives which can be used include, but are not limited to, benzalkonium chloride and edetate disodium.
  • Viscosity modifiers which can be used include, but are not limited to, methyl cellulose, glycerol, and polyethylene glycol.
  • Osmotic agents which can be used include, but are not limited to, sodium chloride, mannitol and sorbitol.
  • Delivery enhancing agents that facilitate the delivery of the therapeutic compound of the invention into the aqueous humor include, but are not limited to, substances which increase corneal permeability, such as surfactants, wetting agents, liposomes, DMSO, and the like.
  • a wetting agent is a substance which facilitates corneal penetration by mildly disrupting the outer corneal surface.
  • a preferred wetting agent is benzalkonium chloride.
  • Other examples of wetting agents include sorbitan esters, polyoxyethylene ethers and the like. These additional materials preferably are present, if at all, in amounts effective to provide the desired benefit or property to the formulation.
  • ophthalmic formulations useful in accordance with the present invention preferably are substantially nonirritating and nondamaging to the eye. Normally, such formulations can be applied in a liquid carrier, with an aqueous carrier being preferred although in some instances, quick dissolving forms of the medicaments may be administered in powder form or rubbed into the eye from applicators of various types. Spraying of the eye, the use of eye drops, and other methods of administration or application can be used.
  • Dosage levels vary greatly depending upon the individual to be treated and the specific medicament used. Proper dosing can be determined without undue experimentation and according to procedures well known to those of ordinary skill in the art.
  • the formulations preferably are packaged as sterile solutions in dropper bottles, as are well known in the trade.
  • Other containers, including eye cups, can also be used.
  • the eye to which the muscarinic component is administered includes an artificial IOL, and in particular an artificial IOL adapted to be axially moved in the eye to provide accommodation.
  • Such accommodating IOLs may include, but are not limited to, the IOLs disclosed in Levy U.S. Patent 4,409,691 and Cumming U.S. Patents 5,674,282 and 5,496,366.
  • the accommodating IOL is adapted for bidirectional accommodating movement, that is both anteriorly and posteriorly in the eye, from an intermediate rest position in the eye.
  • Such an IOL is disclosed in commonly assigned U.S. Patent Application 19980213976 filed December 17, 1998.
  • a base solution can be formulated as follows (percentages by weight/volume (w/v)): sodium chloride 0.3%; edetate disodium 0.1%; boric acid 1.0%; benzalkonium chloride 0.01%; sodium hydroxide (adjust to pH 6.4) and water. Pilocarpine, at a concentration of 0.1% weight/volume, is added to the base solution.
  • the above formulation is administered to the eye of a 50-year old human adult which includes a monofocal IOL adapted to move axially in the eye to achieve accommodation.
  • An increased range of axial movement in the eye, evidenced by an increased degree of accommodation, is apparent after administration of the eye drops.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)
  • Spectrometry And Color Measurement (AREA)
  • Paper (AREA)
  • Furan Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Claims (16)

  1. Utilisation d'un agoniste muscarinique pour la fabrication d'un médicament permettant d'augmenter l'espace disponible dans l'oeil d'un mammifère portant une lentille intraoculaire artificielle, ledit médicament étant efficace, lors de son administration dans ledit oeil, pour augmenter une contraction tonique d'un muscle ciliaire dans ledit oeil, en augmentant ainsi l'espace disponible.
  2. Utilisation selon la revendication 1, dans laquelle le médicament est administré localement dans l'oeil selon une composition ophtalmique pharmaceutiquement acceptable
  3. Utilisation selon la revendication 1, dans laquelle la lentille intraoculaire artificielle est adaptée pour se déplacer dans une direction axiale dans l'oeil pour créer de l'espace disponible.
  4. Utilisation selon la revendication 1, dans laquelle l'agoniste muscarinique est sélectionné parmi la pilocarpine, l'isopilocarpine lactame, le carbachol, le bétanéchol, la métacholine et la muscarine.
  5. Utilisation d'un antagoniste muscarinique pour la fabrication d'un médicament permettant d'augmenter l'espace disponible dans l'oeil d'un mammifère portant une lentille intraoculaire artificielle, ledit médicament étant efficace, lors de son administration dans ledit oeil, pour augmenter une contraction tonique d'un muscle ciliaire dans ledit oeil, en augmentant ainsi l'espace disponible.
  6. Utilisation selon l'une quelconque des revendications 1 ou 5, dans laquelle l'oeil inclut un muscle ciliaire et le médicament est efficace pour augmenter la contraction tonique du muscle ciliaire en étant administré dans l'oeil.
  7. Utilisation selon l'une quelconque des revendications 1 ou 5, dans laquelle le médicament est efficace lorsqu'il est administré localement dans l'oeil selon une composition ophtalmique pharmaceutiquement acceptable.
  8. Utilisation selon l'une quelconque des revendications 1 ou 5, dans laquelle la lentille intraoculaire artificielle est adaptée pour se déplacer dans une direction axiale dans l'oeil pour créer de l'espace disponible.
  9. Utilisation selon la revendication 5, dans laquelle l'antagoniste muscarinique est sélectionné pour agir sur un sous-type de récepteur M1 d'un muscle ciliaire de l'oeil.
  10. Utilisation selon la revendication 9, dans laquelle l'antagoniste muscarinique est sélectionné parmi la pirenzépine, la télenzépine et le trihexyphénidyle.
  11. Utilisation selon la revendication 5 dans laquelle l'antagoniste muscarinique est sélectionné pour agir sur un sous-type de récepteur M2 d'un muscle ciliaire de l'oeil.
  12. Utilisation selon la revendication 11 dans laquelle l'antagoniste muscarinique est sélectionné parmi la (+) (11-({2-[diéthylaminométhyl]-1-piperdidinyl}acétyl)-5,11-dihydro-6H-pyrido-(2,3-b)(1,4)benzodiazépine-6-one et la (+)4,11 dihydro-11-{[(2-[dipropylamino)méthyl]-1-piperidinyl)amino]carbonyl}-6H-pyrido(2,3-b)(1,4)benzodiazépine-6-one.
  13. Utilisation selon la revendication 5, dans laquelle l'antagoniste muscarinique est sélectionné pour agir sur un sous-type de récepteur M3 d'un muscle ciliaire de l'oeil.
  14. Utilisation selon la revendication 13, dans laquelle l'antagoniste muscarinique est sélectionné parmi le méthiodure de diphénylacétoxy-N-méthylpipéridine et le chlorhydrate de (+)p-fluro-hexahydro-sila-difénidol .
  15. Utilisation selon la revendication 5 dans laquelle l'antagoniste muscarinique est sélectionné pour agir sur le sous-type de récepteur M4 d'un muscle ciliaire de l'oeil.
  16. Utilisation selon la revendication 15 dans laquelle l'antagoniste muscarinique est sélectionné parmi la pirenzépine et la télenzépine.
EP00907033A 1999-01-27 2000-01-25 Procedes permettant de retablir ou d'accroitre l'espace disponible lors de conditions pseudo-phakiques Expired - Lifetime EP1148880B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/238,130 US6164282A (en) 1999-01-27 1999-01-27 Methods for restoring and/or enhancing accommodation in pseudo phakia
PCT/US2000/001911 WO2000044379A2 (fr) 1999-01-27 2000-01-25 Procedes permettant de retablir ou d'accroitre l'espace disponible lors de conditions pseudo-phakiques
US238130 2002-09-10

Publications (2)

Publication Number Publication Date
EP1148880A2 EP1148880A2 (fr) 2001-10-31
EP1148880B1 true EP1148880B1 (fr) 2006-12-13

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EP00907033A Expired - Lifetime EP1148880B1 (fr) 1999-01-27 2000-01-25 Procedes permettant de retablir ou d'accroitre l'espace disponible lors de conditions pseudo-phakiques

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Country Link
US (1) US6164282A (fr)
EP (1) EP1148880B1 (fr)
JP (1) JP2002535368A (fr)
AT (1) ATE347889T1 (fr)
AU (1) AU767163B2 (fr)
BR (1) BR0007699A (fr)
CA (1) CA2360685C (fr)
DE (1) DE60032335T2 (fr)
WO (1) WO2000044379A2 (fr)

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US7976577B2 (en) 2005-04-14 2011-07-12 Acufocus, Inc. Corneal optic formed of degradation resistant polymer
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US8911496B2 (en) 2006-07-11 2014-12-16 Refocus Group, Inc. Scleral prosthesis for treating presbyopia and other eye disorders and related devices and methods
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USD702346S1 (en) 2007-03-05 2014-04-08 Nulens Ltd. Haptic end plate for use in an intraocular assembly
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BR0007699A (pt) 2001-11-06
CA2360685C (fr) 2010-03-30
ATE347889T1 (de) 2007-01-15
CA2360685A1 (fr) 2000-08-03
US6164282A (en) 2000-12-26
DE60032335T2 (de) 2007-06-28
WO2000044379A3 (fr) 2000-11-30
EP1148880A2 (fr) 2001-10-31
WO2000044379A2 (fr) 2000-08-03
AU767163B2 (en) 2003-10-30
AU2859800A (en) 2000-08-18
JP2002535368A (ja) 2002-10-22
WO2000044379B1 (fr) 2000-12-28
DE60032335D1 (de) 2007-01-25

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